Background/Purpose: The recent introduction of biologic agents targeting immunologic checkpoints (immunologic checkpoint inhibitors, ICI) established immunotherapy as a highly effective cancer therapy. ICI that trigger an anti-tumor response by activation of T cells, may also cause immune-related adverse events (irAEs). Characterization of rheumatic adverse events such as arthritis and data on treatment of irAEs are scarce. The aim of this study is to characterize patients with new-onset arthritis under ICI therapy and to assess the efficacy and safety of treatment that aimed to balance anti-tumor and anti-inflammatory therapy.

Methods: In this prospective observational study, patients with melanoma or NSCLC receiving ICI therapy who experienced arthralgias were evaluated for the presence of musculoskeletal inflammation. Data on demographics, ICI regime, time of onset and response to therapy of musculoskeletal irAEs, imaging, joint count, CRP/ESR, and immune serology were collected. Further, clinical response to antiinflammatory therapies including NSAR, glucocorticoids (GC) and methotrexate was assessed before and after an antiinflammatory treatment with VAS GH by patients and two expert rheumatologists aware of all clinical data but blinded for treatment, patient identity and study purpose.

Results: Of 10 patients with arthralgias after initiation of ICI therapy, arthritis was demonstrated in 9 patients: 4 monoarthritis, 3 oligoarthritis (SpA pattern), 2 polyarthritis (RA pattern). PMR-like disease with typical ultrasound findings was evident in 1 case and in 3 cases concurrent with arthritis. Upon first visit in our clinic, CRP levels were elevated in 7 of the patients (5.5 to 107 mg/l) while immune serology was positive only in two patients.

The mean baseline VAS GH patient was 7.4 ± 0.9 and was significantly reduced after a median of 24 weeks of antiinflammatory treatment to 2.0 ± 1.3. Initially, all patients were treated with NSAID and/or systemic GC. Six patients received intraarticular GC. Five patients flared on GC treatment upon tapering and were given methotrexate. Remission was achieved in all and prednisolone could be tapered.

Patients were followed for a median of 272 days, and no safety signal with regard to tumor reappearance was detected.

Retrospective analysis of cancer staging imaging studies revealed good sensitivity for PET-CT in the detection of synovitis, as opposed to contrast-enhanced CT.

Interestingly, in one patient low RF and ACPA titers had been detected when she presented with arthralgias without synovitis five years prior. This patient developed highly active RA one day after the first infusion of nivolumab.

Conclusion: Inflammatory manifestations were associated with high disease burden and not self-limiting. In monarthritis, GC joint injection resulted in long-term remission. In oligo- and polyarthritis flares were frequent after tapering and, thus, potential side-effects including attenuation of the antitumor efficacy of ICI are a concern. This is the first report on the efficacy and safety of methotrexate as a GC-sparing agent in ICI-induced arthritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/response-to-methotrexate-and-glucocorticoid-injection-in-new-onset-arthritis-after-checkpoint-inhibitor-therapy/